Abstract 6145: Increased PD-L1 expression levels were observed on both tumor cells and macrophages by tocilizumab plus gemcitabine/nab-paclitaxel treatment in gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer patients
Authors: Kyoko Yamaguchi, Etsuko Fujii, Shuichi Mitsunaga, Noriaki Sawada, Masafumi Ikeda, Takashi Fujitomo, Hideaki Mizuno, Yoko Kayukawa, Mayu Makikawa, Kazunori Aoki, Hiroshi Imaoka, Mitsuhito Sasaki, Kazuo Watanabe, Atsukiko Kato, Hiroyuki Tsunoda, Kimio Terao, Atsushi Ochiai
Journal: Cancer Research (2022)

Abstract Background: Blockade of interlukine-6 (IL-6) and programmed death-1-ligand 1 (PD-L1) limits tumour progression in murine models of pancreatic cancer. When PD-L1 expression of metastatic pancreatic cancer (MPC) is increased under the influence of gemcitabine exposure plus IL-6 inhibition, the spectrum of benefit from immune checkpoint blockade may expand to MPC patients with combined blockade of IL-6 and PD-L1 plus gemcitabine-based chemotherapy. We sought to determine PD-L1 expression of liver metastasis during cycle 1 of a phase I study, tocilizumab (TCZ) plus gemcitabine/nab-paclitaxel (GN) in patient with GN-refractory MPC. Methods: This phase 1 study enrolled 10 patients with MPC that had progressed after GN. All patients experienced cycle 1 of TCZ plus GN, TCZ 8 mg/kg on Day 1 and nab-paclitaxel 100 mg/m2 + gemcitabine 750 mg/m2 on Days 2, 9, and 16. Biopsy of liver metastasis was performed before Cycle 1 and at the end of Cycle 1. Tumour microenvironment including PD-L1 expression were evaluated in paired-biopsied specimen from 7 patients by multicolour immunofluorescence staining. Tumour cell and PD-L1 expression were labelled by anti-cytokeratin 19 antibody and anti-PD-L1 antibody clone SP263, respectively. Cell numbers per millimetre squared (cell density) and the percentage of PD-L1 positive cell in tumor area were calculated according to cell types including tumour cell as cytokeratin 19 positive cell and macrophage as CD68 positive cell. Results: Cell density and the percentage of PD-L1 positive tumor cell were 29/mm2 and 1.1% in mean at baseline and tended to be increased up to 142/mm2 (P = 0.11) and 5.2% (P = 0.06) at the end of cycle 1. Means of PD-L1 positive macrophages were 28/mm2 and 6.9% at baseline and were increased to 69/mm2 (P = 0.01) and 14% (P = 0.08). When region of interest was selected from tumor stroma, differences of PD-L1 positive macrophage during cycle 1 was also maintained in cell density (P = 0.02) and the percentage of PD-L1 positive cell (P = 0.06). Conclusion: TCZ+GN induced an increase of PD-L1 expression levels on tumor cell and macrophages. Citation Format: Kyoko Yamaguchi, Etsuko Fujii, Shuichi Mitsunaga, Noriaki Sawada, Masafumi Ikeda, Takashi Fujitomo, Hideaki Mizuno, Yoko Kayukawa, Mayu Makikawa, Kazunori Aoki, Hiroshi Imaoka, Mitsuhito Sasaki, Kazuo Watanabe, Atsukiko Kato, Hiroyuki Tsunoda, Kimio Terao, Atsushi Ochiai. Increased PD-L1 expression levels were observed on both tumor cells and macrophages by tocilizumab plus gemcitabine/nab-paclitaxel treatment in gemcitabine/nab-paclitaxel-refractory metastatic pancreatic cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6145.